Filtration system for preparation of fluids for medical applications

ABSTRACT

A treatment system for performing a treatment on a patient may include a treatment fluid preparation device having a pump connected by a fluid channel to a reservoir of a source fluid, the pump conveying the source fluid from the reservoir, through a filter, and combining the source fluid with a concentrate by pumping the source fluid with the concentrate to form a treatment fluid in a batch container. The treatment fluid preparation device may have a controller that controls a heater, the pump, and a memory. The controller starts the heater to warm the treatment fluid in the batch container at a time that is responsive to the treatment time stored in the memory. The controller also detects a pressure property of the filter to determine its integrity and outputs an indication of a failed batch if the pressure property indicates the integrity of the filter is insufficient.

RELATED APPLICATIONS

The present application is continuation of U.S. application Ser. No.15/195,801 filed Jun. 28, 2016, which is a continuation of U.S.application Ser. No. 13/968,430 filed Aug. 16, 2013, now U.S. Pat. No.9,388,059 granted Jul. 12, 2016, which is a divisional of U.S.application Ser. No. 13/603,505, filed Sep. 5, 2012, now U.S. Pat. No.8,545,428 granted Oct. 1, 2013, which is a divisional of U.S.application Ser. No. 13/083,915, filed Apr. 11, 2011, now U.S. Pat. No.8,679,348, granted Mar. 25, 2014, which is a continuation of U.S.application Ser. No. 10/585,675, filed Jul. 7, 2006 (§ 371(c) date ofMay 19, 2008), which is a national stage entry of InternationalApplication No. PCT/US2005/00381, filed Jan. 7, 2005, which is acontinuation of International Application No. PCT/US2004/00476, filedJan. 7, 2004, which claims benefit to U.S. Provisional Application No.60/438,567, filed Jan. 7, 2003, all of which are incorporated herein byreference in their entireties.

BACKGROUND OF THE INVENTION

Many medical applications require purified water and other fluids, forexample, hemofiltration, tissue irrigation, and hemodiafiltration. Someprior art systems have focused on continuous purification processes thatrequire a separate filtration/purification apparatus that must beperiodically purged and verified to provide sufficient constant flow ofsterile replacement fluid. (See Chavallet U.S. Pat. Nos. 6,039,877 and5,702,597.) Such devices are necessarily complicated and requireseparate pumping systems for the purification process. In addition, therate of supply of fluid for such systems is very high, requiringexpensive filters to be used. The same high-rate problem exists for thegeneration of replacement fluid for hemofiltration, and therefore alsorequires expensive filtering apparatus.

Large and small scale inline systems are known for preparation ofinfusible fluids and for preparation of dialysate. The following priorart references discuss examples of such systems.

U.S. Patent Publication No. 2004/0232079

U.S. Patent Publication No. 2003/0105435

U.S. Pat. No. 5,645,734

U.S. Pat. No. 5,782,762

U.S. Pat. No. 6,136,201

PURELAB Maxima, Ultra-Pure Water Purification Systems

Shipe, Brad; “The Case for UV in Dechlorination Applications,” WaterConditioning & Purification Magazine, January 2003, Vol. 45, No. 1

During hemofiltration, hemodialysis, hemodiafiltration, ultrafiltration,and other forms of renal replacement therapy, blood is drawn from apatient, passed through a filter, and returned to the patient. Dependingon the type of treatment, fluids and electrolytes are exchanged in thefilter between a dialysate and/or extracted from the blood byfiltration. One effect may be a net loss of fluid and electrolytes fromthe patient and/or exhaustion of dialysate, with a concomitant need forits replenishment, again depending on the type of treatment. To replacefluid lost from the patient and keep the patient from dehydrating,replacement fluid may be injected into the patient at a rate thatmatches a rate of loss, with an adjustment for a desired net change inthe patient's fluid complement. To replace exhausted dialysate, freshdialysate is continuously circulated through the filter.

Conventionally, dialysate and/or replacement fluid is supplied fromeither of two sources: batches of fluid, typically in multiple bags, ora continuous source of water that is sterile-filtered and added toconcentrated electrolytes to achieve the required dilution level.Because replacement fluid is injected directly into the patient,replacement fluid must be sterile. When either method is used togenerate replacement fluid, there is a risk of contamination of thefluid. Contamination may occur, for example, at the point where bags offluid are accessed (“spiked”) or at any connection in the fluid circuitlinking the source to the patient.

In many instances, such therapies may require a large quantity ofsterile fluid. A typical way to provide the large quantity ofreplacement fluid is to provide multiple bags of replacement fluid,dialysate, or infusate. The connection of these bags of fluid to anextracorporeal blood circuit, there is a risk of touch-contaminationresulting in the introduction of biological contaminants into thefluids. Presently, methods of producing large volumes of dialysate fromtap water are known, but each requires complex water purification andstandardization equipment, since impurities and cleaning additives suchas chlorine vary greatly in tap water from municipality to municipalityand within a municipality over time. (See Twardowski U.S. Pat. Nos.6,146,536 and 6,132,616.) Moreover, dialysate solution, whether preparedonline or prepackaged, while of the proper concentration for use as asterile replacement fluid, never enters the patient's body. Instead,dialysate flows past a semipermeable membrane that permits ions to beexchanged across the membrane until a balance between theirconcentrations in blood and their concentrations in the dialysis isachieved. This is effective to remove impurities from the blood and toadd missing electrolytes to the blood. Because it does not have to beinfused, dialysate is less expensive than solutions prepared asreplacement fluids, which are injected directly into a patient.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A illustrates fluid preparation apparatus embodiments in afigurative way for discussing various features and arrangements of amedical fluid purification system.

FIG. 1B illustrates a filter device with control elements that provideassurance of fluid quality and prevent breakthrough of contaminationupon filter expiration.

FIGS. 2A and 2B illustrate a filter and batch container with connectorsystems that ensure against contamination.

FIG. 3 illustrates a self-clamping connector.

FIG. 4 illustrates a batch container tubing set.

FIG. 5 illustrates a fluid preparation apparatus embodiment in afigurative way for discussing various features and arrangements of awater purification system.

FIGS. 6, 7, and 8A illustrate portions of an embodiment of a fluidpreparation apparatus.

FIG. 8B illustrates a portion of a filter module in which two redundantultrafiltration membranes are commonly housed.

FIGS. 9A and 9B illustrate embodiments of a batch container.

FIG. 10A illustrates a fluid quality sensor such as a conductivity orresistivity sensor configuration for sensing fluid quality in acontainer.

FIG. 10B illustrates a medicament concentrate cartridge.

FIG. 11 illustrates a filter module in partial ghost perspective view.

FIG. 12 illustrates a filter cartridge with an expansion device.

FIGS. 13A and 13B illustrate fluid preparation devices for use with areplaceable filter module such as the one illustrated in FIG. 11.

FIG. 14 illustrates a control system to support features of variousembodiments.

FIG. 15 is a flow chart for discussing various control options of thevarious embodiments discussed herein.

FIG. 16 illustrates a treatment environment for use of a controlembodiment.

FIGS. 17, 17A, and 18 illustrate ultrafilter configurations that aretolerant of the evolution of air from within the ultrafilter.

FIG. 19 is a schematic illustration of a standalone/retrofit apparatussystem for batch filtration of a sterile replacement fluid.

FIG. 20 is a flow chart illustrating an exemplary control procedureapplicable to various embodiments of the invention including those ofFIGS. 19 and 21.

FIG. 21 is a schematic illustration of a blood treatment machine with anattached subsystem for batch preparation of sterile replacement fluid.

FIGS. 22A and 22B are illustrations of fluid filters that may be use invarious embodiments of the invention.

FIG. 23 illustrates an exemplary blood treatment system with a filterused to sterilize and/or degas replacement fluid during treatment.

FIGS. 24, 25, and 26 illustrate a blood treatment machine and cartridgeproviding various supporting mechanical features for the embodiment ofFIG. 23 and further embodiments, including one in which a quality ofreplacement fluid is sensed before infusion.

FIG. 27 illustrates a disposable fluid circuit kit which may supportvarious embodiments of the invention.

FIG. 28 illustrates a set up for priming a blood treatment process,which components of the invention may be used to support.

FIG. 29 illustrates a portion of a blood treatment machine that allows apump used as part of the blood treatment to also be used to control thefiltering of fluid to provide a batch of infusible replacement fluid.

DETAILED DESCRIPTION

The present disclosure relates to apparatus, methods, devices, articlesof manufacture, etc. for producing pure water and, in some embodiments,pure solutions. These may be used for the preparation of solutions formedical applications such as tissue irrigation, preparation ofpharmaceutical, blood treatments such as hemofiltration, hemodialysis,hemodiafiltration and ultrafiltration, and other treatments.

As described in FIG. 1A, to supply suitable water that is substantiallyfree of unwanted dissolved and undissolved materials, a combination ofpermanent and replaceable components may be provided at the treatmentsite. FIG. 1A is an overview of a framework that provides benefits,particularly in certain environments. One such environment is renalreplacement therapy. Patients must be treated at least twice a week andoften daily. On the other hand, excellent sterility design urges the useof pre-sterilized throw-away components to ensure against various modesof contamination which need not be enumerated. But replacing everycomponent that must be contamination-free upon every use is profoundlyexpensive, particularly where treatments are done every day. Prior artapproaches have addressed this problem by combining permanent componentswhose sterility is guaranteed by intensive sterilization procedures,some of which are backed up (made failsafe) by using additionaldisposable components that are used once and discarded. Alternatively,the disposable can be made more robust to avoid the on-sitesterilization procedures. But this presents the problem of forcing thedesigner to use inexpensive, and therefore less desirable components inthe disposable portions, or of simply imposing the burden of high coston the medical treatment system.

FIG. 1A shows a new model that compromises on this point and isconsidered particularly applicable in the renal replacement therapyenvironment. A permanent module 920 has certain pretreatment componentsthat may be used repeatedly without replacement and withoutsterilization and includes filtration and treatment steps that are notunduly inclined to aggravate, or susceptible to, contamination. Examplesare illustrated in the further embodiments. This permanent module may bedesigned to receive variations of water quality. A semi-permanent module922 provides more than one use, for example a month's worth of uses, butis disposable periodically or upon detection of incipient failure. Thepermanent module may contain a controller to enforce the proper use andhandling of the semi-permanent module since safeguards must be enforcedwith regard to it. But with the semi-permanent modules, as discussedbelow in connection with particular embodiments, the procedures do notinvolve washing, cleansing, sterilization. The final stage includesfinal filtration and/or treatment steps provided in a single-use element924. In the final stage, the least expensive components may be arrangedto guard against sterility failures of the upstream components. As willbe seen, the preferred embodiments described herein conform to thismodel. Variations of the model are possible including fragmenting theintermediate modules into ones used according to other schedules such asone module replaced monthly and another replaced weekly. An example of asemi-permanent element and a control system to safeguard againstcontamination are shown in FIG. 1B. Note that the embodiment of FIG. 1Bmay constitute an independent invention and need not be employed in acombination as discussed with reference to FIG. 1A, although thisidentified as a preferred configuration. Referring to FIG. 1B, a pump416 feeds raw water into a filter module 425 via an input line 403. Thefilter module 425 contains first and second filters 410A and 410B. In anembodiment, the first and second filter stages 410A and 410B aredeionizing filters. The first and second filter stages 410A and 410B maybe accompanied by other types of filters (not shown here but discussedand illustrated elsewhere in the instant specification) in the filtermodule or externally thereto to perform a complete water treatment.Treated water is supplied to a batch container 417, which may or may notbe present. In the illustrated configuration, water is treated forpreparation of a medicament which may be included in concentrate form inthe batch container 417 as a presterilized consumable unit.

Between the first and second filter stages 410A and 410B, a waterquality sensor 405 is provided. In an embodiment, the water qualitysensor 405 is a conductivity or resistivity probe that detects ionicspecies in the water after passing through the first stage filter 410A.In a preferred embodiment, the second stage 410B provides at least someredundancy in that the second stage 410B provides some of the filtrationeffect of the first stage 410A. In an alternative embodiment it providesall of the filtration of the first stage 410A and is thereby completelyredundant. In such an arrangement, the first stage would expire (becomedepleted), allowing contaminants to break through, before the secondstage expires. The contaminant breakthrough is detected by a controller415 connected to the water quality sensor 405. The controller 415 alsocontrols the pump 416. Upon expiration of the first stage 410A, thecontroller allows the preparation to continue until a certain amount offluid is collected in batch container 417, preferably an amount requiredfor a treatment. Once this threshold quantity is delivered, thecontroller will not allow the pump 416 to be started until the filtermodule 425 is exchanged with a fresh one. The second stage filter 410B,preferably, is sized to ensure that, by itself, it can purify at least asingle batch of water, plus a safety margin without any contaminantbreakthrough to the output line 404. In a preferred embodiment, thesecond stage filter 410B is a smaller size than the first 410A. In thepreferred embodiment, the second stage filter 410B may be of a differenttype which may not be as able to handle high contamination loads as thefirst 410A. This may be acceptable because, although after breakthroughis detected, the emerging fluid is still substantially purified and theload input to the second stage filter 410B may remain low until a singlebatch of fluid is prepared.

In an alternative embodiment, the filter module 425 is provided with apermanently attached data carrier 423 such as radio frequencyidentification device (RFID), bar code (1- or 2-dimensional),contact-type identification device, etc. The data carrier 423 contains aunique identifier of the filter module. When a cartridge is connected tothe pump, the controller 415 reads the data carrier 423 using a readerdevice 422 and stores the identifier in a memory 437. If the waterquality sensor 405 indicates contaminant breakthrough, the controllerpermanently stores the identifier in an expired directory in the memory,which has a non-volatile portion for the directory. If a user attemptsto connect a module 425 with an identifier stored in the directory, thecontroller will not operate the pump and will indicate the errorcondition by means of an annunciator 420 or equivalent device, such asan LCD display message.

Note that in an alternative device, the data carrier 423 is aprogrammable device with a writable memory. In this embodiment, thecontroller 415 programs the data carrier 423 with a flag indicating thatthe filter module 425 is expired. The controller 415 then prevents theinitiation of a new batch.

FIG. 1B also illustrates an optional embodiment with a pressuretransducer 435 that may be used to test for clogging of the first stagefilter 410A. When the pump 416 head pressure reaches a particularmaximum, in order to allow a batch preparation to be completed, thecontroller activates a normally-closed valve 426 to bypass the firstfilter stage 410A. Water flows through a bypass line 427 and through thesecond stage filter 410B. The expiration of the filter module 425 maythen be enforced by the controller in either of the ways describedabove. The above embodiment may be used in filter modules 425 thatcontain filters that clog when depleted such as carbon filters or porousmembrane filters. Not that the clogging and breakthrough devicesdescribed above may be combined or used exclusively in a given filtermodule embodiment. Note also that the head pressure may be sampled andstored over a period of time to determine if the pressure change profileis characteristic of a filter suffering normal usage. This woulddistinguish, for example, an accidental line blockage and preventinappropriate use of the bypass line 427.

Referring to FIGS. 2A and 2B, a multi-use filter device 440 has anoutlet port 441 A with a cap 444A to avoid contamination. The outletport 441A is connectable to a mating port 441B, which is also capped(cap 444B). The ports 441A and 441B may be, for example, locking luerconnectors. A special clamping connector 442, which seals itself whendisconnected from a mating connector 452 is connected to port 441B and aline connecting it to a batch container 450 which receives purifiedwater from the multi-use filter device 440. A microporous filter 453guards against the introduction of contaminants by touch contaminationwhen connectors 441A and 441B are mated.

The special clamping connector 442 may any suitable device that sealsoff, to prevent contamination. An embodiment of such a connector isshown in FIG. 3, although the sealing and disconnecting functions, to bedescribed below, can be performed by separate mechanisms so thisembodiment is not essential. An outlet tube 460 connectable to thefilter 453 of FIG. 2A is permanently affixed to a male luer fitting 478of a male connector 452 that is received by a female luer fitting 479 ofa female connector 442. The female connector 442 has a pair of latcharms 464 that engage a ridge 469 of the male connector 452. The latcharms 464 pivot on living hinges 468 affixed to the female luer fitting479. Pinching ridges 470 and 476 compress the tube 474 when a bendableretaining ring 472 is squeezed. At the same time, engaging ends 466 ofthe latch arms 464 retract from the ridge 469 releasing the male luerconnector 452. The bendable retaining ring 472 retains its deformedshape once it is pinched so that the tube 474 remains pinched andthereby sealed when the connectors 442 and 452 are disconnected. Thebendable retaining ring 472 may be made of ductile metal, for example.The retaining ring 472 may be replaced by another suitable device suchas a ratchet mechanism.

Returning to FIGS. 2A and 2B, when the multi-use filter device 440 isfirst used, its outlet connector 441A is sealed with a cap 444A as isthe inlet connector 442 (with cap 444B) of the batch container 450. Thebatch container 450 may be sealed and sterilized with the specialfitting 442 and its mating connector 452, which may correspond toelements 442 and 452 in FIG. 3, connected in a completely sealed andpre-sterilized state. Other ports such as a sampling port 454 may alsobe sealed and, if only used as outlets, protected from intrusion offluid by means of a check valve 456 and/or another membrane filter 453(not shown separately). The first time the batch container 450 isconnected to the multi-use filter device, the caps 444A and 444B areremoved and the connectors 441A and 441B mated. After filtered water iscollected in the batch container 450, the special clamping connector 442is disconnected and left connected to the multi-use filter device 440 tokeep it sealed and free from contamination as shown in FIG. 2B. Thesecond time the multi-use filter device 440 is used, the specialclamping connector 442 is removed by means of the connector pair 441Aand 441B and discarded while a new batch container's 450 connector 441Bis mated to the pre-existing multi-use filter device's 440 outletconnector 441A. The connector 441B carries a new special clampingconnector 442 and the same process can be repeated.

FIG. 4 shows an embodiment of a batch container, for example one thatmay be used with the foregoing embodiments, but in particular, with theabove embodiments. The batch container 1 has a batch container, proper,1, a break-off female luer lock connector 4, a y-connector, 5, a pinchclamp 6, a male luer 8, a female luer 26, a sterile filter (e.g., 0.22micron pore or pyrogen filter) 11, a non reopenable tubing clamp 13, anon-breathing cap 14 on a female luer 9. Line 15 has an in-line checkvalve 16, a pinch clamp 18, a break-off male luer cap 25 and female luer19, and a female luer 21. Various tubing branches 3, 7, 10, 12, 15, 17,and 20 connect these elements. The batch container 1 is delivered to apatient treatment setting as a sealed sterile container with allterminals sealed. The batch container 1 may contain, as delivered, aconcentrate solution sufficient to create a treatment batch of fluid,such as 5 dialysate or replacement fluid, when water is added.Concentrate may be added by means of the luer connector 21. In thetubing set delivered to the treatment site, the tubing branch 20 may besealed and cut after the concentrate is added. Water is added at thetreatment site through connection to a water source via luer 9. Thewater is preferably metered to provide a predefined quantity. The osterile filters should be sufficient to protect against contamination bypyrogens before water is added to the batch container 1. A sample ofdiluted treatment fluid may be drawn through the luer 19 beforetreatment. The check valve 16 prevents any contamination due to backflowfrom the sampling procedure. After water is added to the treatment fluidcontainer 1, the luer 9 is disconnected from the male luer 8 and themale luer connector connected to the blood treatment system. Luerconnectors are shown by way of example as are other features and theseare not essential to all embodiments.

FIG. 5 illustrates another arrangement of a particular embodiment whosedescription follows. A pretreatment module 900 provides primaryfiltration from a raw water supply, for example tap water and feedsprefiltered water to a controller module 905 which provides variouscontrol functions, a pump, pressure detection and control, and permanentfiltering capabilities which are not shown separately here. Water ismetered by the control module into a consumable disposable module 910which may provide deionization, adsorption filtration, microporousfiltering, chemical pretreatment, etc. and any other types of filteringthat may require replacement of components. The purified water isfinally conveyed to the batch container circuit 915 discussed withreference to FIG. 4.

Referring to FIG. 6, pretreatment module 900 is shown in more detail. Acheck valve 955 prevents backflow. An air vent 953 removes air from theprimary supply and a sediment filter 951 (which may be replaceable)provides substantial filtering of solids.

Referring to FIG. 7, the control module 905 is shown in greater detail.A shutoff valve 1010 is provided for safety. Pressure indicators 1015and 1025 may be provided for monitoring the respective pressures in andout of a pump 1020. Feedback regulation may be provided to ensure thatconsistent metering is provided if the pump is relied upon for measuringthe total quantity of water supplied to the batch container 1. A highintensity ultraviolet (UV) lamp 1031 provides a both sterilizationmechanism and a mechanism for removing chlorine and chloramines.Preferably, the UV lamp 1030 is of such intensity and wavelength as toprovide disintegration of chloramines. In a preferred embodiment, thelamp is characterized by a 245 nm wavelength and an output power of 750mJ/cm2 up to 1500 mJ/cm2 which is sufficient to remove chloramines. Byoxidizing chloramines and subsequently, as described below, filteringusing a deionizing filter, chloramines can be removed.

Note that pressure indicators 1015 and 1025 may be pressure transducersthat feed control signals to a control device such as discussed withreference to FIG. 1B and to be discussed with reference to FIGS. 13A and13B. The operation of pump 1020 may be controlled in dependence onpressure indications from such transducers. For example, if a high headpressure is indicated, an alarm may be indicated and the pump shut down.This may indicate a problem with a connected filter. Also, the pump maybe operated for a short interval and a pressure decay profile recordedand compared with an expected decay profile. If the profile does notmatch, it could be used to indicate a leak (such as in a filter or line)or a clog in the system. If the upstream pressure goes low, it couldmean that the water supply is turned off or some other fault. Each ofthese events may be indicated by means of an annunciator or display(e.g., see 330 and 380 at FIGS. 13A and 13B and attending discussion)and/or by switching off the pump to avoid damage to the system and tonotify the operator to take corrective action.

Referring to FIG. 8A, the replaceable (disposable or remanufacturable)filter module 910 contains a first stage filter 1007 copper-zinc alloywhich is used to subject the water to a reduction/oxidation process toremove ions. This removes ions through a chemical reaction. Anembodiment is KDF 85 media where about one pound is used for a flow rateof 150 ml./min water flow rate. An activated carbon filter 1005 followswhich is a well-known adsorption type filter. Next three stages ofstrong acid cation (SAC) 1011 and strong base anion (SBA) 1009 filtersfollow in series. The SAC/SBA filter cartridges 1011/1009 are not mixedbeds as typically used in water filtration applications. They separatethe cation and anion stages as illustrated because it has beendetermined to be much more effective at removing colloidal aluminum fromthe treated water. Note that the order of the SCA and SBA beds is notlimited to what is shown and that they can be housed in a singlecanister or multiple canisters. Also note that other components can besequenced differently as well as should be clear from this disclosure.For example, it should be clear that the pump 1020 can be used in apushing arrangement to draw water through the UV lamp and theparticulars of the arrangement are not limiting to the inventionsdisclosed. Also note that the resistivity probe 1022 can be includedwithin a single deionizing filter between previous and followingdeionization stages and employed to similar effect. In such anembodiment, a deionizing filter would have leads or contacts to connectthe probe to an external measurement device or controller.

Note that instead of using layered beds in a single cartridge asdescribed, separate cartridges each containing one of a SBA and SACfilter bed may be used. Also, each cartridge could contain more than onelayer of each to provide similar results.

The resistivity probe 1022 detects ion concentration by contact testingof the resistivity of the water. A signal is generated to indicate thatthis will be the last allowed batch before the system will require thereplacement of the replaceable module 910. Control may be provided as inthe embodiment of FIG. 1B, discussed above. The second filter in thepresent embodiment, which backs up the first stage suffering frombreakthrough, is a mixed bed deionization filter 1031. This ensures thatthe current batch can be completed. A second, final safeguardresistivity or conductivity test is provided with an audible alarm at1025 as a back-up safety measure. If the value it detects is above acertain level, the pump 1020 may be shut off and an alarm sounded. Thismay come into play if the resistivity probe 1022 fails, or if thesafeguards discussed with reference to FIG. 1B are breached. TP is ahydrophobic membrane air vent which allows air in ultrafilters 1035A and1035B to be purged. The ultrafilters 1035A and 1035B may be amicrotubular filter such as used for dialysis. An air vent may also beprovided as shown at 1047. The air vent may, for example, have a 1.2micron hydrophilic membrane that blocks air. There is a hydrophobicmembrane port which allows air to vent from the filter. These areavailable as off the shelf components. Any suitable air eliminationdevice may be used and these features are non-limiting of the describedembodiments. Also, the second stage MBDI type filter 1031 can be alayered deionization filter such as 1002C with the same benefits asdescribed in terms of providing protection against breakthrough. Also,the final resistivity sensor 1025 can be located as shown or moved toanother location downstream of the final deionization stage, such asafter or between the ultrafilters 1035A and 1035B, and the configurationshown is not limiting of the invention.

Note, it should be clear that resistivity probe 1022 may be used in aconfiguration such as that of FIG. 1B, with the resistivity probe 1022corresponding to sensor 405 such that filter module 910 corresponds tofilter module 425.

Note that two separately-housed ultrafilters 1035A and 1035B areserially interconnected. The separate housings ensure against failuremechanisms such as grow-through of pathogens, adjacent simultaneous orshared seal failure. For example, prior art reference U.S. PatentPublication No. 2003/0105435, cited in the Background section, shows afilter cartridge with two microporous membranes in adjacent layers of afilter cartridge housing. These may share a seal mechanism or adjacentseals such that failure of the seal of one necessarily involves failureof the seal of the other. Also once a grow through problem occurs inone, the adjacency may cause the problem to creep directly into theadjacent membrane. These problems are prevented by the illustratedarrangement of separate redundant ultrafilters.

Note that the benefit of separately housed filters may be substantiallyprovided in a single housing by substantially separating two ultrafilterlayers. Referring to FIG. 8B, for example, a multilayer filter withvarious types of filter elements housed in a common cartridge 1052contains two ultrafilter layers 1050A and 1050B. The cartridge may be asdescribed in U.S. Patent Publication No. 2003/0105435, which is herebyincorporated by reference as if fully set forth in its entirety herein.The two ultrafilter layers 1050A and 1050B, separate membranes, are keptapart by an intermediate layer 1056, which may be a spacer or anotherfilter medium. Separate seals 1057A and 1057B, which are also spacedapart, are provided.

Note the final conductivity/resistivity sensor/alarm 1025 may controlthe pump, as noted. A controller 1090 may be connectable to thedisposable filter module 910 and configured to stop the pump 1020. Thetrigger resistivity safety level to cut-off the pump 1020 may be 1megohm, but may be raised to 2 megohm to allow the use of requiredtemperature compensated resistivity probes (an FDA & AAMI requirement)This does allow use of low cost in-line resistivity probes in thedisposable filter module 910.

Preferably, the filter module 910 as well as the modules of otherembodiments are of such a flow rate that upward flow of fluids ispossible. Generally, prior art deionization beds suffer from the problemof floating or loosening resin particles which may have been disturbedduring handling. The separation and floating of the particles breaks upthe beds and renders the filters less effective. To avoid this,generally, filter systems are configured to direct flow downwardlythrough the beds to help keep and compress the resin particles. But ifflow rates are kept low, as may be done in the present system, water maybe flowed in an upward direction which helps to eliminate air fromstream. Air is a notorious problem in the preparation of medicamentssuch as dialysate. The precise flow rates needed to allow upward flowwill vary according to the characteristics of the system. One way toallow faster flow rates without being hampered by break away resinparticles is to provide a bed compressor of resilient porous material tocompress the bed. Referring momentarily to FIG. 12, in a filtercartridge 1150, a resilient compression layer 1140 urges the filtrationmaterial 1145 in a downward direction. The resilient compression layermay be any suitable polymeric or rubberlike material that is compatiblewith the application.

The following is an example procedure for using the devices discussedwith reference to FIG. 4.

1. Remove the dialysate concentrate tubing set 915 and remove the cap 14from the tubing line 7 that contains the filter 11. (The 0.22 micronfilter 11 provides additional protection from inadvertentcontamination.)

2. Connect the outlet line 404 to the concentrate bag luer connection 9.

3. Break the frangible luer connector 4 which connector is configured toform a permanent seal on the side facing the Y-junction 5 whendisconnected.

4. Add predetermined quantity of water into the concentrate bag usingthe purification plant through tubing branch 7 through luer connector 9.

5. Optionally a user can write on the bag label the date and time waterwas first added to the concentrate bag, to assist in ensuring that it isused within a period of time. An automated scheme may be employed aswell.

6. Shake the batch container 1 well to mix.

7. Confirm solution conductivity prior to use. Remove the break-off cap1 and draw sample from this branch 15. After removing the sample, clampthe line using the pinch clamp 17 provided.

8. (The following is normative according to a preferred embodiment andnot limiting of the invention) Conductivity must be in the range 13.0 to14.4 mS/cm. Nominal conductivity for the dialysate solution is 13.7mS/cm at 25° C. If conductivity does not meet this specification do notuse it. Verify that the results are accurate. If conductivity is highadditional water may be added to bring it within specification. Ifconductivity is low then the solution must be discarded.

9. Using the non re-opening clamp 13 provided, clamp the line that isconnected to the water purification plant.

10. The clamp 6 is, next, clamped on the line that is connected to thedialysate bag 1.

11. Disconnect the water source at the luer connection 26.

12. Connect the bag of dialysate solution to the dialysis circuit at theconnection 8. This leaves the filter 11 and permanent clamp 13 in placeto protect the water supply source.

13. Unclamp the line going to the dialysate bag using clamp 6, andinitiate treatment after verifying that dialysate will be used within 24hours from when water was added.

Referring to FIGS. 9A and 10A, a batch container 100 has a fluid qualitysensor 135 of a probe 120, such as a contact-type conductivity sensor.The latter may simply be two metallic surfaces separated by a knowndistance and of a given area that has been calibrated. A cage 135 in asupport 105 sealed to the wall 130 of the batch container 100 which maybe a polymer bag as typically used in the medical industry. The cage 135prevents an opposing wall (not shown separately) from preventing fluidfrom circulating around and through the cage and in contact with theprobe such that a reading of the probe 120 is improved. The probe 120extends from the support 105 and has a lead 122 with a signal connector125 that can be connected to a controller (discussed later). The probe120 is an independent element and can be used with any of theembodiments so its description here in combination with other featuresis not intended to be limiting. Note that preferably, the probe assemblyis permanently sealed to the batch container such that there is nopossibility that contaminants can enter the batch container 100interior.

At 110, a fitting connecting a sample or feed line 145 is shown. Thelatter may be used, with a connector 156, connect a sampling syringe todraw out a sample of a medicament or infusate. A check valve may beprovided at 155 to prevent ingress of contaminants. A clamp (not shownseparately) may be provided as well to guard against contamination. Inan alternative embodiment, line 145 may be configured for injecting asoluble concentrate into the batch container 100 before the container100 is sealed and sterilized as a unit (for example, by gamma raysterilization). When a prescribed quantity of purified water is added tothe batch container, the diluted concentrate may form a medicament orinfusate such as replacement fluid for hemofiltration or a dialysate forhemodialysis. Line 145 may also represent a draw line that may beconnected to a treatment machine. In the latter case, a sterile filter(at 155), such as a microporous membrane of 0.2μ may be provided toguard against touch contamination. Additionally, a clamp may be providedas at 155.

In the embodiment of FIG. 9A, purified water may be added to the batchcontainer by another instance of a line similar to 145. Alternatively,if concentrate or other medical solute or medication is contained in aseparate container, such may be added to the batch container 100 bymeans of a double lumen spike 174. (Details of a suitable dual lumenspike can be found in US Patent Publication No. 2004/0222139, which ishereby incorporated by reference as if set forth in its entiretyherein). A spikable bag 170 contains, for example, medical fluidconcentrate such as concentrated dialysate. Purified water is pumpedthrough connector 182 of line 180 and passed into the bag (afterspiking) by the dual lumen spike 174. The fluid circulates in the bagcarrying its contents back through the dual lumen spike 174 through line172, through a filter 150 into the batch container. The dual lumen spikemay be sealed by means of a removable cap 175 so that the batchcontainer and fluid lines can be sealed and sterilized and laterdelivered as a unit without contamination. Clamps 157 may be provided toseal the batch container 100. A special clamping connector may beprovided and used (for example, special clamping connector 442 asdiscussed with reference to FIG. 2B) in line 180. If concentrate ispresent in the batch container 100 rather than using a spiking bag 170,the concentrate may be used to obtain a data point for a calibrationline fit for measuring fluid conductivity.

Referring to FIG. 9B, instead of providing a conductivity or resistivitysensor in the batch container 100, a dual lumen takeoff 255 with acommon lumen (Y-configuration) 260 housing a water quality sensor 262 ofa probe 210 with corresponding signal connector 220 and lead 215. Asyringe port 240 and check valve 242 are connected inline to the otherbranch of the Y-junction. When a syringe (not shown) is attached andfluid drawn into it, fluid from the batch container passes over thewater quality sensor to allow its quality to be measured. In otherrespects the elements of FIG. 9B are the same (and identically numbered)as those in FIG. 9A.

Referring to FIG. 11, a replaceable multiple use filter module 1125 asmay be used in the various embodiments described herein has an inletport 1130 and an outlet port 1110. A physical arrangement of filtercartridges 1111 is shown which provides for a compact module 1125 thatis advantageous for packaging and assembling to a chassis (as discussedrelative to FIGS. 13A and 13B). Tubing 1116 runs from the top of eachcartridge 1111 to the bottom to provide upward flow as discussedearlier. A signal port 1100 for reading fluid quality sensors 1115 and1105 is provided in a housing. 1127. Signal port 1100 may have a leadwire and connector installed to it or one may be provided separately.Alternatively, signal port 1100 may be a wireless port powered by abattery. Signal port 1100 may include a data carrier as discussed withreference to FIG. 1B or a data carrier may be provided separately orwithout the signal port if a fluid quality sensor is not provided.

A data carrier may include software and instructions for using thefilter module 1125. These may be read by a permanent component of afiltering system as described in connection with FIGS. 13A and 13B. Abase unit 335 may be configured substantially as described withreference to FIG. 5 with the base unit 335 housing the components of thepermanent pretreatment module 900 and controller module 905. The baseunit may contain a display 330, such as an LCD display. Instead of, orin addition to, a display, the base unit (and other embodimentsdescribed herein) may have a voice generator or other type of outputdevice. An inlet port 341 may be provided for receiving raw water to befiltered and an outlet port 340 for attachment to a filter module (whichmay be multi- or single-use) which is received in a locating station315. The latter may have a reader 311 to read a data carrier or toconnect with a fluid quality probe such as one or more conductivitysensors described above. A further locating station may be provided suchas 305 for a batch container. This may have a data carrier reader 320and/or various other components (at 321) such as a heater, a mixer, suchas a moving field generator for magnetohydrodynamic mixing of thecontents of an installed batch container. The base unit 335 may have aport 310 for connection to a fluid quality probe of the batch container.This may provide a calibration input as well as a final measurement offluid quality. The embodiment of FIG. 13B additionally provides alocating station for a concentrate container such as 170 described withreference to FIGS. 9A and 9B. The base unit 335 may further be fittedwith a controller containing a computer with a connection to theInternet or other network connecting the base unit with a server 390.

In an embodiment, features indicated at 301-306 may be added to allowthe base unit 335 to control when and whether an outlet line of a batchcontainer should be opened and clamped. A batch container is fitted inthe station 305 and an outlet line of the batch container fitted betweenclamping portions 303 and 304. A detector 306 verifies that the line hasbeen fitted in place. When the system is run, an actuator 302 and motor301 may be activated to clamp the line during fluid purification and asthe batch container is filled. After the batch is filled, the clamp mayremain closed until a treatment operation, which may be run while thebatch container remains in place, is begun. At treatment time, the clampmechanism 303 and 304 can enforce the expiration time of the batch offluid. For example, a timer can be started within the controller of thebase unit or, equivalently, a time/date stamp stored and the clamp onlyreleased if the batch of fluid is used for treatment within a certainperiod of time. For this purpose a treatment machine and the base unit335 may be combined into a single device under common control or the twomay be linked by a data link to operate cooperatively to achieve such aresult. The flow chart of FIG. 15 describes the control steps involved.

Referring now to FIGS. 9A and 10B, instead of a concentrate container inthe form a spikable bag 170 as illustrated in connection with FIGS. 9Aand 9B, a cartridge 271 as illustrated in FIG. 10B may be used. Here,concentrate 280 is within a sealed cylinder 274 with a piston 273 and aburstable seal membrane 275. The cartridge may be fitted in the baseunit 335 (FIGS. 13A and 13B) which may contain a linear drive 270 andplunger 272 to push the piston 273 thereby bursting the seal membrane275 and inject contents into a T-junction 278 in the path of purifiedwater sent into the batch container 100. Note that the cartridge 271 maybe provided as part of the sterile batch container fluid circuit shownin FIG. 9B.

Referring to FIGS. 14 and 15, the base unit 335 and corresponding partsof other embodiments described herein, may contain a programmablecontroller including an embedded computer 600 with memory, non-volatilestorage, communication elements, etc. Various sensors 605 such asdiscussed in connection with various embodiments may be connected toprovide input to the controller executing a program stored in memory.The latter may be stored in firmware or obtained from a data carrier viaa data port 610 as described previously. In addition, a network orInternet connection to a server 625 may be provided to obtain andtransmit data such as software, instructions for use, expiredidentification codes, etc. Actuators 615 such as valve clamps, pumps,and annunciators 620 such as alarms may be provided as well.

A sample program for operating the various embodiments described hereinis shown in FIG. 15. The process may begin with firmware until softwareloaded at a later stage takes over. Software may be read from a dataport or data store and instructions for using the system output at stepS5 whereupon the system waits for user input. The instructions mayindicate to press hard or soft key to continue at which point steps S10and S15 are executed to determine if a no-go condition exists. If anecessary component (S10) has not been connected, step S30 will beexecuted and the system may output an appropriate message to instructthe user to take corrective action and wait for response. Similarly, ifin step S15, it is determined that a component is expired, such as abatch bag that has been previously used or a filter module has been usedand previously indicated as having suffered breakthrough, step S30 willbe executed. At step S20, various system tests may be performed such asa pressure profile test or quality test. Tests may also includedetermining if the conductivity indicated by a connected conductivityprobe is within specified limits. In step S25 it is determined if alltests have been passed and control passes to step S35 where fluidpreparation is begun. If not, step S30 is performed and appropriateoutput is generated on a display such as 330. If a value goes out ofrange at step S40, control passes to step S60 to determine if anexpiration event has occurred, for example, breakthrough of contaminantsin a filter module. Note that Filter modules may be “stamped” with apermitted time of use after a first use when presumably the seal wasfirst broken. This may be enforced in the same manner as discussed withreference to attempted reuse of a filter module after breakthrough wasdetected. Thus, step such an event may be detected at step S60 as well.

At step S55 depending on the type of data carrier (e.g., programmable orjust carrying a unique ID), the expired or spent unit is indicated asexpired so that reuse can be prevented. For example, in S55 the datacarrier may be programmed with a token to indicate that the attachedfilter module is expired or a server may be sent a message to indicatethat its unique ID should be added to a list of expired IDs. Anysuitable device may be used to “expire” a unit. Since expiring a unitmay still allow a batch to be prepared, control returns to S40.Completion of the treatment may be determined at step S45 by measuringthe total mass pumped or by other means. For example, if the embodimentprovides a conductivity probe in the batch container, step S45 maydepend on the measured conductivity of the batch contents. Oncecompletion is determined, the system may be halted at step S50 and thebatch bag “stamped” with a time and date. Note that further instructionsmay be output at this point.

In one embodiment, the water purification and treatment may be done froma single apparatus and under common control. The steps following stepS50 illustrate this. Assuming purified fluid has been added to a batchcontainer of some description such as those described in the currentspecification or some other, the contents of the container may be mixed,if a solute is involved, and the contents checked in some way in stepS51. For example, the conductivity of a mixed batch or the resistivityof a pure batch can be checked determine its conformity with treatmentspecifications. In step S52, if a value is out of range, control passesto step S30, but if not, the batch may be utilized at any time up to anexpiration time/date (MTU time, or Mixed Till Use-time). In step S53, anoutlet clamp that prevents fluid from being drawn from the batchcontainer is released to allow a treatment to be performed with thefluid product. At the same time, an acceptance message can be output tothe user on a display. At this time, in S54, a time stamp is stored or atimer started to keep track of the expiration of the batch of fluid. Ifthe expiration is not observed, which is tested at step S56 by checkingto see if the timer has expired, the clamp will close in step S30 (underthe general step indicated as “take action”) and an appropriate messageoutput. The system will then wait until treatment is completed while,optionally, continuously checking the MTU timer in steps S46 and S56.

Note that many of the described mechanical and control features arenovel and inventive alone, as subcombinations with other features andtheir description in combination in the above embodiments is notintended to be interpreted as limiting of the inventions disclosedherein. Referring to FIG. 16, when a treatment machine 700 attempts touse a batch container 710 tagged with an expiration date at step S50, itcan determine if the date has passed and prevent use of an expired batchcontainer thereafter. This may be implemented with contact or wirelessdata reading devices, a programmed smart card type device or via anInternet server as described with reference to the mechanism forenforcing non-reuse of filter modules.

Referring to FIG. 17, air may evolve from fluid as it passes through anultrafilter 714. Preferably, the ultrafilter 714 has a high membranesurface and in such filters, the potential for air evolution may befairly high. To avoid problems with bubbles forming in the filter, theembodiment of FIG. 8A shows transducer protectors TP, which arehydrophobic air vents. But the lines leading to them can fill with waterand render them useless for air purging. A refinement of theconfiguration of FIG. 8A, which may be used in any water treatment plantas a final protective stage, is to provide an ultrafilter 714 (which maybe a standard dialyzer capped at the lower blood port) with an inlet 712and outlet 704 on one side of the membrane connected by a return line704 flowing through an air filter/vent 706, through further line 708into a T-junction 717 and back into the inlet line 712. Ultrafilteredfluid is drawn out through line 707. Again, the filter/vent 706 may be a1.2 micron air vent with a 1.2 micron hydrophilic membrane that blocksair and a hydrophobic membrane port which allows air to vent from thefilter. These are available as off the shelf components. The watercolumn defined by line 708 is denser than the corresponding columnwithin the housing of ultrafilter 714 so that a return flow will existthrough the branch 704, 706, 708. The reason for the lower density isdue to the evolution of air in the ultrafilter 714.

An alternative design that integrates air vent configurations into thehousing of the ultrafilter 714 is shown in FIG. 17A. For the outlet(filtrate) side of the media, an air vent, e.g., a hydrophobic membranetype air vent 765 may be integrated into the outlet of an ultrafilter715 and an air filter such as a hydrophilic air filter membrane 766integrated into the outlet. Any bubbles coming out of fluid collect atthe top of the filtrate side (in a header space of a microtubularmembrane type filter) and be vented by the hydrophobic air vent 765. Onthe inlet side of the ultrafilter 715 (the side of the filter media thathas not yet been ultrafiltered), air collecting in the inlet side willleave by an air vent 467, for example one using a hydrophobic membrane469. A check valve 742 may be provided to prevent siphoning and/orreduce risk of contamination.

Referring to FIG. 18, to address any problem with inadequate flowthrough the return branch of the FIG. 17 embodiment, a resilient channelelement 730 such as an inline bladder 731 may be included with checkvalves 724 and 728. When the system pumps fluid, the resilient channelelement 730 stores fluid under pressure and releases it in pumpingfashion when the system stops pumping. Again, an air filter/vent 724allows air to escape and purged from the return line 726. The returnflow problem can also be dealt with by replacing the T-junction 717 witha Venturi device configured to create a suction in line 708 by using anaccelerated fluid flow through the line 714,712.

One of the drivers for the features discussed above is a need to providepure water irrespective of input water quality. The above embodimentsare not reliant upon water quality and are designed to reliably producepure water or solutions regardless of input water quality. Variousembodiments are also designed to reduce the costs associated with lowervolume (10-60 liters) preparation of medical and other pure solutionsand to maintain simplicity through the combination of semi-permanent andsingle-use modules which combine to eliminate the complexities, costsand safety issues associated with maintenance, sterilization, andoperation of many other prior art systems.

Referring to FIG. 19, a filter 2160 filters fluid from a source of fluid2150 to generate a batch of sterile replacement fluid 1302. The filter2160 may be, and preferably is, a microporous filter that blocks allmaterials except dissolved electrolytes and water. Thus, the result ofthe filtration process is to sterilize the raw fluid from the source offluid 2150. The source of fluid 2150 may be a container of sterile ornon-sterile replacement fluid, one or more containers of constituentswhich, when combined, form a proper replacement fluid. Any of the lattermay include a continuous source such as a water tap. One or more conduitelements form a line 120 to convey the source fluid 2150 through thefilter 2160 and into a batch container 2147. The latter may be any typeof sterile, preferably disposable container, for example, a large INbag. It may also include a number of such containers appropriatelyinterconnected to permit flow into and out of them in the fashion ofcontainer 2147.

Included in the conveyance from source fluid 2150 to sterile replacementfluid 1302 may be a pump 2190, such as a peristaltic pump. The pressureat an outlet of the filter 2160 may be sensed by a pressure sensor 2162and the pump 2190 controlled by a controller 2170 to insure a predefinedtransmembrane pressure (TMP) threshold of the filter 2160 is notbreached. The TMP may be maintained at a maximum safe level to maximizethroughput. Note that complexity may be avoided if the source fluid 2150is arranged such as to maintain a desired TMP at the filter 2160 withoutthe need of a pump 2190 or pressure sensor 2162. For example, the sourcefluid 2150 may be provided by a batch container elevated at a certainheight to provide a desired head. Note that a control valve 2165 or aspeed of the pump 2190 may be used to regulate the flow rate to maintaindesired TMP limits.

A control/shutoff valve 2180 may provide the controller 2170 the abilityto stop the flow of fluid through the filter 2160 once a desired volumeis reached. A heater 2185 may be provided to warm the sterilereplacement fluid 1302 to prepare it for use. An insulated container2145 may be used to reduce heat loss so that heater 2185 can be arelatively low power type. The heater 2185 may be controlled by thecontroller 2170 to ensure the replacement fluid 1302 is at a desiredtemperature when required to be used. Alternatively the heater 2185 canbe controlled by an independent device actuated by, for example, apressure sensor (not shown) triggered by the flow of fluid into thebatch container 2147, a timer (not shown) settable to trigger based on apredefined treatment time, or some other means. Preferably, in eithercase, a temperature regulator (e.g., a temperature sensor 183 combinedwith logic in controller 2170) regulates power to the heater to ensure arequired temperature is maintained and not exceeded. The temperaturesensor 183 may be used to sense the quantity of sterile replacementfluid by the rate of detected temperature increase versus heater output.The temperature sensor 183, heater 2185, and sterile replacement fluid1302 can be modeled in any desired fashion. For example one may neglectall but the thermal mass of the RF, assume perfect heat transfer(including assuming the RF fluid to be isothermal). Then, the mass wouldbe given by the product of the temperature change, the thermalcapacitance of the fluid, and the heat output rate of the heater. Morecomplex theoretical or empirical algorithms would be a simple matter toderive and implement. Once the mass of fluid is calculated to be below acertain level, the controller 2170 may be programmed to respond inaccord with the assumption the sterile RF is exhausted. Equivalently,the controller 2170 may simply respond to some predefined rate oftemperature rise of the temperature sensor 183. When the temperature ofthe sterile replacement fluid 1302 is raised, dissolved gas may come outof solution. This may cause bubbles to accumulate inside the replacementfluid container 2247, which is undesirable because of the risk ofinfusing bubbles into the patient's bloodstream. To help ameliorate thatproblem, a vibrator or ultrasonic transducer may be provided 183 tocause bubbles to coalesce and rise to a top of the container 2147. As aresult, bubble-free replacement fluid may be drawn through the outlet2148.

A connector 2195 may be provided for connecting the source fluid to theline 120. The connector may be a luer, spike, threaded adapter, or anyother suitable type. Although the various controls indicated above areshown to be controlled an automatic controller 2170, each may becontrolled also by manual mechanisms.

The FIG. 1 embodiment allows replacement fluid to be prepared in batchfor later use. Thus, the rate of filtration of replacement fluid neednot match the requirements of the treatment process or preparatory stepssuch as priming. As a result, a low capacity filter may be used for thefilter 2160. For example, typically only a small quantity of expensivemedia is required to make a small-capacity filter and as such, the costof a low capacity filter can be much smaller than a high capacityfilter. Also, other features found in high capacity filters, such as alarge ratio of media surface to volume of the filter module areachievable only by means of folding or forming media into shapes thatcan be difficult to manufacture, such as tubes. Thus, savings can beachieved in simplification of the configuration of the filter as well.Relatively small filters with simple planar media held in plasticcasings are available and suitable for this purpose.

The configuration of FIG. 19 may be retrofitted for use with an existingtreatment system. For this purpose, the outlet 2148 may provide with anyrequired connection adapter. A user interface 2175 for entering datainto the controller 2170 may be provided as well.

Referring now to FIG. 20, a control algorithm for controlling the heater2185, pump 2190, valves 2165/2180, etc. begins with the a setting of atime for treatment S 10, for example by entering a time into thecontroller 2170 via a user interface (UI) 2175. The time can be enteredmanually or automatically by means of, for example, a data signal from aremote source via a switched or network circuit. The time for treatmentmay be obtained from a treatment calendar entered into the controller2170, which also may be obtained from a remote source. In the presentsimple algorithm, first and second time intervals T1 and T2 are definedrepresenting the interval required for filtration of RF and the intervalrequired for heating of RF, respectively. These values may be obtainedfrom any of the above means (e.g., local manual or remote entry viaUI/interface 2175) or from data encoded on one of the consumablesinvolved in the process. For example, the filter 2160, the RF fluidcontainer 2147, the source fluid 2150 container(s), or any otherconsumable may be provided with one or more bar-codes, RFID tags, orother suitable encoding device. Such devices may provide values for TIand T2, tables of values that depend upon other factors, or other datafrom which TI and T2 may be derived. The controller 2170 waits until itis time to start the flow of raw RF fluid from source fluid 2150 towardcontainer 2147 by comparing a current time (indicated by a clockinternal to the controller 2170, which is not shown) to a differencebetween a scheduled treatment time and TI, which represents the leadtime (ahead of the scheduled treatment) required for the filteringprocess. A loop through step S202 is exited to step S302 when the clockreaches the treatment time minus TI. At step S302, the flow of sourcefluid 2150 through the filter 2160 is initiated. If the pump 2190 ispresent, it may be started and regulated according to a specified TMP.The latter may be provided to the controller 2170 manually orautomatically through UI/interface 2175. Automatic entry may be by wayof a data store such as bar-code or RFID attached to the filter, forexample which may be read when the filter 2160 is installed in a chassiswith a corresponding reader device (not shown). Note, as mentionedabove, the source fluid may be sterile and the filtration processprovided as a guarantee against contamination, for example by accidentaltouching.

Once the flow of source fluid 2150 is initiated, the controller waitsfor the required time for applying power to the heater 2185. The delayand the initiation are controlled by step S402 which is exited to stepS502 only when the treatment time minus the predefined interval T2 isreached. As mentioned above, alternatively, the heater may be triggeredby detecting fluid such as by means of a sensor (not shown) triggered bythe presence of sterile replacement fluid 1302 in the container 2147.The sensor may be any of a variety of types, such as an ultrasonicsensor, capacitance sensor, mass sensor, optical sensor, etc.

Once the heater is started, the controller 2170 may wait for the sourcefluid to be exhausted at step S602. Step S602 exits to step S702 whenthe source fluid is determined to be exhausted. The latter may bedetected by integrating the flow rate to measure the total volume (therate may be determined by the pumping rate, for example, or by a flowmeter (not shown)). The exhaustion of the source fluid 2150 may also beindicated by a quantity indicator (e.g., a level indicator) in thesterile replacement fluid container 2147 or an intermediate containersupplied through a drip chamber, for example. Alternatively, theexhaustion of the source fluid 2150, if supplied from a fixed-volumecontainer, may be indicated by a sensor such as an ultrasonic sensor,capacitance sensor, mass sensor, optical sensor, a scale, etc. Yetanother alternative is to sense gas or a precipitous rise in negativepressure (sensed by a pressure sensor which is not shown) at the pump2190 inlet. At step S702, the line 120 may be clamped by actuatingshutoff/control valve 2180. Additionally, if appropriate, the pump 2190may be deactivated at the point where the exhaustion of the source fluid2150 is detected at step S702.

According to an embodiment, as the fluid is pumped, the TMP of thefilter, as indicated by pressure sensors 2162, may be monitored. If theTMP is determined by the controller 2170 to be, at any point, below apredetermined nominal value or to have changed precipitously duringfiltration, the controller 2170 may trigger an alarm or take some otheraction to insure that the resulting replacement fluid is handledappropriately. For example, a back-up filter could be added duringtreatment as discussed with respect to FIG. 23. The TMP results couldtrigger an alarm at any point during filtration or could be assessed andreported at step S702, before treatment would begin.

The controller 2170 pauses again at step S802 to wait for the sterilefluid to be exhausted. This may be indicated by a signal from thetreatment machine (e.g., received via UI/interface 2175) or by directmeasurement by a sensor, such as an ultrasonic sensor, capacitancesensor, mass sensor, optical sensor, a scale, etc. As mentioned above,the controller 2170, or the heater 2185 itself, may be provided with athreshold temperature-rise rate that indicates the mass of fluid in thereplacement fluid container 2147 has fallen below a minimum level. Theloop of step S802 is exited to step S902 where power to the heater 2185is terminated.

Note that all the functionality attributed to the controller 2170 may beprovided, via a control interface, by a controller (not shown) internalto a treatment machine. For example, the apparatus of FIG. 19 could beprovided as an optional module for such a treatment machine rather thana retrofit module. Referring now to FIG. 21, a combination bloodtreatment system and sterile replacement fluid device 2310 has areplacement fluid preparation subsystem 2305 configured substantially asthe device of FIG. 19. A filter 2260 filters fluid from a source offluid 2250 to generate a batch of sterile replacement fluid 2230 as inthe embodiment of FIG. 19. Again, the source of fluid 2150 may be acontainer of sterile or non-sterile replacement fluid, one or morecontainers of constituents which, when combined, form a properreplacement fluid and any of the latter may include a continuous sourcesuch as a water tap. A line 2220 conveys the source fluid 2250 throughthe filter 2260 and into a batch container 2247, which may be any typeof sterile, preferably disposable container, for example, a large INbag. It may also include a number of such containers appropriatelyinterconnected to permit flow into and out of them in the fashion ofcontainer 2247.

Again, a pump 2290 may be provided and pressure at an outlet of thefilter 2260 may be sensed by a pressure sensor 2262. The pump 2290 maybe controlled by a controller 2270 to insure a maximum safe TMP tomaximize throughput. Again, the pump 2290 is not required and the sourcefluid 2150 may be arranged such as to maintain a desired TMP at thefilter 2160 without the need of the pump 2290 or pressure sensor 2262 byelevation. A control valve 2265 or a speed of the pump 2290 may be usedto regulate the flow rate to maintain desired TMP limits. Acontrol/shutoff valve 2280 may provide the controller 2270 the abilityto stop the flow of fluid through the filter 2260 once a desired volumeis reached. A heater 2285 may be provided to warm the sterilereplacement fluid 1302 to prepare it for use. An insulated container2245 may be used and the heater controlled as discussed with respect tothe FIG. 19 embodiment. Bubbles may be controlled, as discussed above,by means of a vibration or ultrasonic transducer 2230 as discussed abovewith regard to the previous embodiment.

A connector 2295 may be provided for connecting the source fluid to theline 2220. The connector may be a luer, spike, threaded adapter, or anyother suitable type. Although the various controls indicated above areshown to be controlled an automatic controller 2270, each may becontrolled also by manual mechanisms. Other aspects of the controlmechanisms for the embodiment of FIG. 21 may be provided as discussedwith respect to FIGS. 19 and 20.

The benefits of the FIG. 20 embodiment are similar to those of the FIG.19 embodiment in that it allows replacement fluid over a time periodthat is not driven by the speed of supply to the treatment process. As aresult, a low capacity filter may be used for the filter 2260 with theattendant benefits identified above. Note that the UI/interface 2275 andcontroller 2270 are shared in the present embodiment by the treatmentmachine. Thus, any information required for control of both thetreatment and preparation of sterile replacement fluid 2230 would notneed to be communicated to a separate controller such as controller2170. Note also that the communications among the illustrated componentsis provided by a channel 2202 which may be wire harness, separate wires,a bus, a wireless channel or any suitable communications/powertransmission device. In the embodiment of FIG. 21, a predicted quantityof replacement fluid may be filtered and stored for use duringtreatment. If, however, for some reason, more is required, the treatmentmachine controller 2270 could be configured to identify that situationand control the subsystem 2305 components to provide it. Many bloodtreatment process employ a filter 2220 to filter blood and into whichreplacement fluid is supplied to a patient 2225. More details onpreferred embodiments of the treatment machine are discussed below.

In either of the above embodiments, the rate of flow of fluid duringpreparation of the batch of replacement fluid may be substantially lessthan the rate of consumption during treatment. In an exemplaryembodiment of an application for hemofiltration, the amount ofreplacement fluid consumed is between 9 and 18 1. and the rate ofconsumption is approximately 200 ml./min. Also, the media used forsterile filtration may be any suitable media that insures the quality ofthe replacement fluid is as desired. In the embodiments discussed above,it was assumed that the end sought was preparation of sterilereplacement fluid employed microfiltration to prevent the passage ofpathogens. However, the invention could be used with other types offiltration or treatment processes to produce a batch of fluid consumedby a medical treatment process, for example, dialysate for hemodialysistreatment. The benefits accrue in particular when the time scale ofpreparation may be longer than the time scale of consumption. Moreover,the benefits are more appreciable when some sort of energy-consumingprocess is required, such as heating, before consumption. Here, not onlyis the time scale of preparation compatible with a small inexpensivefilter, but the long time scale permits heating of the replacement fluidover a long interval. To support this benefit, the batch container maybe insulated to minimize heat loss so a small heater will be adequate.Also, the preferred application for the present invention is in thecontext of hemofiltration because the quantity of fluid required forsuch treatment is relatively small.

Note that other motivations for filtering the fluid, in addition to oras an alternative to sterilization of a non-sterile fluid, is (1)removal of air bubbles and/or (2) as a safety net for ensuring againstaccidental contamination. If bubble removal is the only concern, a dripchamber may be used instead of a filter. For removing bubbles, thefilter preferably is of a type that permits the passage of fluid, butwhich blocks the passage of bubbles, for example due to its media poresize and the surface tension of the fluid. Referring now to FIG. 22A, apreferred type of filter for some of the present embodiments has aninlet port 2415 providing an inlet channel 2410 communicating with aninlet chamber 2440. An outlet leading port 2405 provides an outletchannel 2420 communicating with an outlet chamber 2445. A piece offilter media 2425 separates the inlet and outlet chambers 2440 and 2445.The fluid to be sterilized enters the inlet chamber 2440, is sterilizedby passing through the filter media 2425, and exits via the outletchamber 2445. A gas relief gasket 2425 allows gas accumulating in theinlet chamber 2440 to be released to the ambient atmosphere. Internalsupports and structural details are not shown in the illustration forclarity, but a practical embodiment of the filter of FIGS. 22A and B mayhave ribs for strength and internal supports for the media 2425 andgasket 2425 so that the filter 2400 may be capable of tolerating asubstantial TMP.

The gas relief gasket 2425 may be of a porous hydrophobic material suchas PTFE. Air bubbles trapped in the inlet chamber 2440 can coalesce inthe inlet chamber 2440 and exit via the air relief gasket 2425. It maybe, depending on the type of gas relief gasket 2425 used, that asubstantial TMP will be required to eliminate air.

An alternative to the gas relief gasket 2425 is a gas relief valve 2426as shown in FIG. 22B. Since the inlet chamber 2440 is connected to thenon-sterile side of the filtration system, there is little risk ofcontamination if microbes were to enter through a mechanical device suchas the gas relief valve 2426. The latter is illustrated figuratively andallows only gas to escape. Other features of the embodiment of FIG. 22Bare labeled with the same numerals as features of the embodiment of FIG.22A where they serve substantially identical functions and, thus, theirdescriptions are not repeated here.

Referring now to FIG. 23, the filters of FIGS. 22A and 22B may be usedfor filtration of replacement fluid in the embodiment of FIG. 23 asdiscussed presently. Replacement fluid 2360, which may or may not besterile, is supplied to a hemofiltration machine 2490. A replacementfluid pump 2360 pumps the replacement fluid into a balancing mechanism2330 which meters the replacement fluid before it is introduced, via ajunction 2485, into the venous (return) line 2480 and ultimately intothe blood stream of a patient 2225. Waste fluid is drawn through a wasteline 2470 from a filter 3952 and pumped via a waste pump 2365 throughthe fluid balancing mechanism 2330. The fluid balancing mechanism 2330meters the replacement fluid to match the rate of withdrawal of wastefluid so that the patient's fluid balance is maintained duringtreatment. Actually, the rate of withdrawal of waste fluid may be lessthan the rate of metering of replacement fluid by pumping waste fluidthrough a bypass pump called an ultrafiltration pump 2339. The lattersends some of the waste fluid directly to a waste fluid sump 2380,thereby bypassing the fluid balancing mechanism 2330. The fluidbalancing mechanism is depicted figuratively and may operate in accordwith any suitable control device. Preferably it meters replacement fluidon an equal-volume or equal-mass basis. A preferred mechanism isdescribed in U.S. patent application Ser. No. 09/513,911, filed Feb. 25,2000, entitled: “Synchronized Volumetric Fluid Balancing Systems andMethods,” which is hereby incorporated by reference as if fully setforth in its entirety herein. Various sensors and line clamps, indicatedfiguratively at 2335, 2355, 2320, 2385, and 2390, may be provided tocontrol flow and ensure safe operation.

A filter 2337, is provided in the replacement fluid line 2338 justupstream of the junction 2485. The filter 2337 may serve as a lastchance safety net for ensuring that replacement fluid is sterile and/orthat all bubbles are removed before flowing into the venous line 2480.To ensure that air is not infused into the patient's body, an air sensor2390 is often provided in hemofiltration systems, but detection of airnormally triggers an alarm, automatic shutdown, and skilled interventionto restart the hemofiltration treatment. Obviously, this is undesirableso the system should, as effectively as possible, insure that air orother gas is not injected into the venous line 2480.

Although in the embodiment of FIG. 23, a hemofiltration machine wasdiscussed, other types of treatment processes may be provided alast-chance filter similar to filter 2337. For example,hemodiafiltration, hemodialysis, or other treatments may require theinfusion of replacement fluid and thereby benefit from a filter such asfilter 2337. Preferably, the filter 2337 is substantially as in theembodiment of FIG. 22A. Thus, the filter 2337 removes both air andpathogens.

Instead of employing a filter at the location indicated at 2337, a dripchamber may be used. Suitable drip chambers are currently available withair vents and microfilters effective to remove pathogens, so they may besubstituted for the filter 2337. Also, in some cases, it may be thatthere is very little risk that the replacement fluid is contaminatedwith pathogens, the filter 2337 may serve as a mechanism for removingonly air or other gases. In such cases, drip chambers which remove gas(either with or without a vent), could be employed at the above locationin the fluid circuit.

Referring now to FIGS. 24, 25, and 26 the last chance filter or dripchamber (or combination device) 2510 may be installed in a cartridge2520 that holds and orients blood and fluid circuits for ahemofiltration machine 2540. In the embodiment shown, which is describedsubstantially in U.S. patent application Ser. No. 09/513,773 filed Feb.25, 2000 and entitled: “Fluid Processing Systems and Methods UsingExtracorporeal Fluid Flow Panels Oriented Within A Cartridge,” herebyincorporated by reference in its entirety as if fully set forth herein,fluid circuit components may be held in a cartridge 2520 and clamped (asshown in FIG. 26 with the machine closing as illustrated by the arrow2665) within a receiving gap 2530 in a blood treatment machine such ashemofiltration machine 2540. The cartridge 2520 may have a preferredorientation which may insure a correct orientation for the last chancefilter or drip chamber (or combination device) 2510 if required by theparticular device chosen. To insure orientation of the last chancefilter or drip chamber (or combination device) 2510, the latter ispreferably held by the cartridge 2520 in a fixed orientation withrespect to the cartridge 2520.

In an alternative embodiment, the last chance filter or drip chamber (orcombination device) 2520 may be accompanied by a device 2660 formeasuring the quality of the replacement fluid, such as conductivity ordensity. This may provide a last-chance check that the replacement fluidis of the correct type. For example, where such fluids are derived frommixtures, if the proportion is not exactly what is required, infusioncould be harmful to the patient 2225. An example of a device 2660 totest the fluid could be a wettable pair of contacts (not shown) formedin a tubing set 650 of the cartridge may be used in conjunction with aresistance measurement device to measure the ion concentration of thefluid. Alternatively, a non-wettable sensor, such as an ultrasonicconductivity cell could be used. Other kinds of fluid quality sensorscould be employed such as new types of specific-molecule detectors builton silicon wafers. Preferably, the tubing set 650 and cartridge 2620 ofwhich it is a part form a disposable component that is used for onetreatment and disposed of. Note that the fluid quality sensor 2660 maybe used alone or together with the last chance filter or drip chamber(or combination device) 2510. Note, although FIGS. 6 and 7 are detailed,they are intended to show various components figuratively and do notreveal the details of the routing necessary to achieve the flow pathsdiscussed with respect to them or as illustrated elsewhere.

Referring now also to FIG. 27, the tubing set and cartridge assembly2610, discussed previously, may incorporate the batch replacement fluidcontainer 2625 as part of a sterile replaceable set 2690. The filter2615 may have a tube 2622 with a connector 2620 for attachment to asource fluid 2250. A tube 2635 may connect the filter to the batchreplacement fluid container 2625, which may be fitted with another tube2630 to convey fluid to the tubing set and cartridge assembly 2610.Referring now also to FIG. 28, the batch replacement fluid container2625 may also be fitted with additional connectors 2670 and/orextensions (not shown) to permit the batch replacement fluid containerto be used for priming blood, replacement fluid, and/or waste lines. Forexample, as discussed in U.S. patent application Ser. No. 09/905,246,filed Jul. 12, 2001, entitled: “Devices and Methods For SterileFiltering of Dialysate,” which is hereby incorporated by reference as iffully set forth in its entirety herein, replacement fluid is circulatedthrough a replacement fluid container 2740 to flush air out of all thefluid circuiting (not all shown) of a blood treatment apparatus 2710. Asdescribed in detail in the '246 application incorporated by referenceabove, the venous (return) and arterial (supply) blood lines 2725 and2730 may be temporarily connected via connectors 2750 to the replacementfluid container 2740 and fluid circulated through the container 2740until gas bubbles are substantially purged from the relevant circuits.Note, the replacement fluid container 2740 corresponds to the containers2147 (FIG. 19), 2247 (FIG. 21), and 2625 (FIG. 27) in the foregoingfigures and to respective containers in the application incorporated byreference immediately above. The air and other gases may settle in thereplacement fluid container 2740 as the fluid circulates. Liberation ofthe gases would ordinarily be promoted by the application of heat from aheater 2775 (with power source 2770), which may be employed as discussedwith regard to the embodiments of FIGS. 19-21 or in any suitable way tobring the temperature of the replacement fluid to body temperature.Replacement fluid circuits including line 2735, blood circuits includinglines 2725 and 2730, and waste fluid circuits including line 2780 mayall be flushed with fluid from the container 2740. The details of theblood treatment apparatus and its internal plumbing can vary.Replacement fluid may be transferred from the replacement fluid line2735 or from the blood line 2735 to the waste line, for example througha filter, to flush the waste portion of the circuit including the wasteline 2780. Replacement fluid may circulate through the blood circuitincluding lines 2725 and 2730 as indicated to flush the blood circuit,at least a portion of which may be closed as indicated by the arterialand venous lines 2730 and 2735.

Disposable components, such as the circuit sets of FIGS. 26 and 27 orthe batch replacement fluid container 2625 alone, or other componentsthat may be used with the embodiments disclosed may be packaged withinstructions for preparing infusible replacement fluid. For example, thesource fluid 2150/1250 or a concentrate which may be mixed to make thesame (FIGS. 19 and 21) may be supplied with instructions for sterilefiltering the fluid as described in the instant specification. Such mayconstitute packages of consumables or reusable components. Note thatbenefits of the filtering method and apparatus discussed above may bestbe achieved by performing the filtration just prior to treatment,although this is not required. The filtering method may be performed atthe treatment site. For example, non-sterile concentrate may be storedat the residence of a patient. The concentrate may be diluted withdistilled water in a source fluid container (e.g., 2196 of FIG. 19) atthe residence and processed as discussed in the instant application.Because the infusible fluid is generated at the treatment site, the needfor regulatory-cleared fluids, such as might be obtained from amanufacturer, is not avoided. Cost savings and storage-space economiescan thus be realized by the patient. This is particularly important inview of the fact that renal replacement therapies are often administeredmany times per week and storage and cost of consumables can present aserious problem in a residence or any other facility.

Referring now to FIG. 29, a blood treatment machine, a portion of whichis illustrated figuratively at 2810, may permit a pump 2845 that, duringtreatment, conveys replacement fluid to a patient, to be used forfiltering a sterile filtering a non-sterile source fluid. Here, themachine 2810 has a common guide 2850 that accommodates a fluid line 2815through which fluid is conveyed by the pump 2845, for example aperistaltic pump. During treatment, the line 2815-2825 may be guided bya first selected guide 2830 in a first direction toward other componentsof an internal fluid circuit (not shown) as indicated at 2825. Duringsterile-filtering, fluid may be pumped by the same pump 2845 through aline 2815-2820 that is allowed to pass out of the blood treatmentmachine 2810 via a different guide 2835. This allows the line 2815-2820to be fed to an external connection to the sterile fluid container (notshown) as indicated at 2820.

Although the foregoing inventions have, for the purposes of clarity andunderstanding, been described in some detail by way of illustration andexample, it will be obvious that certain changes and modifications maybe practiced that will still fall within the scope of the appendedclaims. For example, the devices and methods of each embodiment can becombined with or used in any of the other embodiments. For anotherexample, the air vents described can be of any suitable description andneed not be membrane type air vents at all, although these arepreferred.

What is claimed is:
 1. A system for generating a batch of a treatmentfluid at a point of use and for performing a treatment on a patient, thesystem comprising: a peristaltic pump; a disposable cartridge connectedto a fluid circuit that includes a water source line, a filter modulecontaining a first filter stage upstream of a second filter stage, thesecond filter stage providing redundant filtration to the first filterstage; a connecting fluid line configured to receive concentratedtreatment fluid from a concentrate container, a batch container, and asampling line all fluidly connected by one or more fluid lines of thefluid circuit; and a conductivity sensor fluidly connected to the batchcontainer through the sampling line; controllable actuators configuredto selectively open and close and thereby start and stop fluid flow; anda controller configured to control the controllable actuators and theperistaltic pump to perform a dilution function of the concentratedtreatment fluid that forms the treatment fluid in the batch container.2. The system of claim 1, wherein the treatment fluid is dialysate. 3.The system of claim 1, wherein the controller includes a memory, and thecontroller is further configured to store in the memory a uniqueidentifier of the filter module.
 4. The system of claim 3, wherein thecontroller is further configured to detect contaminant breakthroughbased on a signal from a water quality sensor disposed between the firstfilter stage and the second filter stage, to permanently store theunique identifier of the filter module with the contaminantbreakthrough, and to prevent operation of the peristaltic pump when thefilter module having the permanently stored unique identifier isconnected to the system.
 5. The system of claim 1, wherein thecontroller is configured to measure a conductivity of the treatmentfluid with the conductivity sensor connected through the sampling line.6. The system of claim 5, wherein the controller is configured tomeasure the conductivity of the treatment fluid before performing thetreatment on the patient.
 7. The system of claim 1, further comprising:a user interface connected to the controller, the user interface beingconfigured to receive user input specifying a treatment time.
 8. Thesystem according to claim 1, wherein the first filter stage is a firstdeionizing filter.
 9. The system according to claim 8, wherein thesecond filter stage is a second deionizing filter.
 10. The systemaccording to claim 9, further comprising: a water quality sensor fluidlyconnected along a fluid path between the first filter stage and thesecond filter stage, wherein the water quality sensor detects ionicspecies in water that has passed through the first filter stage andbefore the water passes through the second filter stage.
 11. The systemaccording to claim 1, wherein the second filter stage is smaller thanthe first filter stage.